ADAR2-dependent A-to-I RNA editing in the extracellular linear and circular RNAs. (October 2019)

• Record Type: Journal Article
• Authors: Hosaka, Takashi; Yamashita, Takenari; Teramoto, Sayaka; Hirose, Naoki; Tamaoka, Akira; Kwak, Shin
• Is Part Of: Neuroscience research. Volume 147(2019)
• Page Start: 48
• Page End: 57
• Publication Date: 2019-10
• Subjects: ALS amyotrophic lateral sclerosis -- A-to-I RNA editing adenosine-to-inosine conversion of RNA -- ADAR adenosine deaminase acting on RNA -- CNS central nervous system -- Q/R glutamine/arginine -- AMPA α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid -- AR2 mice conditional ADAR2 knockout mice -- VAChT vesicular acetylcholine transporter -- TDP-43 transactive response DNA-binding protein -- WT wild type -- circRNA circular RNA -- hADAR2 human ADAR2 -- siRNA small interfering RNA -- K/E lysine/glutamic acid -- CYFIP2 cytoplasmic fragile X mental retardation interacting protein 2 -- TMEM63B transmembrane protein 63B -- LDH lactate dehydrogenase -- R/G arginine/glycine -- T/A threonine/alanine -- FUS fused in sarcoma -- CSF cerebrospinal fluid; Amyotrophic lateral sclerosis (ALS) -- RNA editing -- Adenosine deaminase acting on RNA 2 (ADAR2) -- Biomarker -- Extracellular RNA -- Circular RNA; Neurosciences -- Research -- Periodicals; Neurosciences -- Research -- Japan -- Periodicals; Neurology -- Periodicals; Neurosciences -- Periodicals; Neurosciences -- Recherche -- Périodiques; Neurosciences -- Recherche -- Japon -- Périodiques; Neurosciences -- Research; Japan; Periodicals; 612.8
• DOI: 10.1016/j.neures.2018.11.005
• Languages: English
• ISSNs: 0168-0102

Abstract

Graphical abstract: Highlights: ADAR2-dependent A-to-I conversion occurs in extracellular RNA as intracellular RNA. ADAR2 mediates A-to-I conversion of intracellular and extracellular circular RNA. ADAR2-dependent A-to-I site in extracellular RNA would be a biomarker of sporadic ALS. Abstract: Currently, no reliable biomarkers of amyotrophic lateral sclerosis (ALS) exist. In sporadic ALS, RNA editing at the glutamine/arginine site of GluA2 mRNA is specifically reduced in the motor neurons due to the downregulation of adenosine deaminase acting on RNA 2 (ADAR2). Furthermore, TDP-43 pathology, the pathological hallmark of ALS, is observed in the ADAR2-lacking motor neurons in ALS patients and conditional ADAR2 knockout mice, suggesting a pivotal role of ADAR2 downregulation in the ALS pathogenesis. Extracellular RNAs were shown to represent potential disease biomarkers and the editing efficiencies at their ADAR2-dependent sites may reflect cellular ADAR2 activity, suggesting that these RNAs isolated from the body fluids may represent the biomarkers of ALS. We searched for ADAR2-dependent sites in the mouse motor neurons and human-derived cultured cells and found 10 sites in five host RNAs expressed in SH-SY5Y cells and their culture medium. Of these, the arginine/glycine site of SON mRNA was newly identified as an ADAR2-dependent site. Furthermore, we detected a circular RNA with an ADAR2-dependent site in the SH-SY5Y cells and their culture medium. Therefore, the changes in the editing efficiencies at the identified host RNA sites isolated from the body fluids may represent potential biomarkers of ALS.